Is ATRN p.Ala45= (c.135C>G) pathogenic?

ATRN p.Ala45= (c.135C>G) is classified Likely benign in ATRN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). Ultra-rare (popmax 0.0357%, afr).

How common is ATRN p.Ala45= (c.135C>G) in the general population?

ATRN p.Ala45= (c.135C>G) is ultra-rare (popmax 0.0357%, afr) (gnomAD).

ATRN p.Ala45=

c.135C>G · rs1002500321 · VCV2420981

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP 1.3, phastCons 1
Overall
CADD	13.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% African / African-American · 24/67,234 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.0018% 26/1,444,460 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0357%	2,801
Remaining individualsnot grpmax-eligible	0.00358%	27,942

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ATRN
Protein: p.Ala45=
Coding: c.135C>G
MANE Select: NM_139321
dbSNP: rs1002500321
Type: single nucleotide variant
Location: chr20:3471242 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27

Full ATRN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATRN p.Ala45Thr Uncertain significance ★ ⚠ same residue
ATRN p.Ala438Gly Uncertain significance ★★ ⚠ same type
ATRN p.Ala87Val Uncertain significance ★★ ⚠ same type
ATRN p.Arg1417Gln Uncertain significance ★★ ⚠ same type
ATRN p.Arg173His Uncertain significance ★★ ⚠ same type
ATRN p.Asn1035Ser Uncertain significance ★★ ⚠ same type
ATRN p.Asn213Ser Uncertain significance ★★ ⚠ same type
ATRN p.Asn300Thr Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/atrn-p-ala45 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown